Radioactive labeling is one of the most sensitive analytical strategies for the detection of chemical compounds. However, applications of this approach in biochemistry are often subject to significant constraints. In vivo radiolabeling may be complicated by radiation damage to cells and by competition from intracellular pools of precursors. In vitro radiolabeling, while producing much higher specific radioactivities, often results in undesired chemical modification of the original compounds which may greatly complicate their separation and identification unless radiolabeling is carried out after separation of the original compounds.
Schmeiser et al have suggested that one general method for such post-separation labeling is the neutron activation analysis, Angew Chem., 65:490-491 (1953). This technique is based upon selective induction of radioactivity in some of the atoms of the elements making up the sample by irradiating the sample with neutrons and then measuring the radioactivity of newly formed unstable isotopes in the sample. In the "direct labeling" method of post-separation detection via neutron activation, one or more of the elements present in the separated compounds of interest are directly converted into their radioactive isotopes by irradiation with neutrons in situ. In one early application of this approach, phosphorus (.sup.31 P)-containing compounds such as phospholipids, have been detected after their separation by paper chromatography using neutron activation to convert .sup.31 P into radioattive .sup.32 P, Strickland et al, Arch. Biochem. Biophys. 88: 344-348 (1960); Nahayama et al, Acta. Chem. Scand. 15: 1595-1603 (1961); Blomstrand et al, J. Neurochem. 8: 230-233 (1961); Robinson, Canad. J. Biochem. 9: 21-34 (1964) and Johnson et al, J. Res. 6: 435-427. However, this technique has limited applicability and sensitivity primarily due to the low neutron activation cross-section of phosphorus. It would be desirable to provide a labeling technique which is much more sensitive and more generally applicable than the direct labeling method.